Clinical Genomic Testing

Question 1

examples of non targeted CYTOGENETIC testing

Question 2

examples of targeted cytogenetic tests

Answer 2

looks at specific chromosome

FISH
RAD (done automatically with CVS or amniocentesis)

Question 3

examples of non targeted molecular testing

Answer 3

molecular = gene

whole genome seuqencing

Question 4

targetd examples of molecular tests

Answer 4

sanger sequencing (CFTR mutation)

PCR testing (fragile X)

metylation sensitivity testing (Prader willi)

Question 5

hromosome Microarray: Genome wide scan looking for deletions and duplication

Identified copy number variation (CNV): for most chromosome regions, we have 2 copies. Missing region (1 copy only) = deletion, extra region (3 copies)= duplication.

Two main types: array CGH, or SNP array → compares the amount of chromosome material to a normal standard

What are the limitations to this?

Answer 5

Limitations: does not detect balanced rearrangements with normal amounts of chromosomes (reciprocal translocation, robertsonian translocations), does not detect other common genetic causes of the disease, does not explain the mechanism of the chromosome abnormality.

Pros: significantyl higher resolution than a karyotype. Allows more diagnoses in individuals with developmental delay, congenital anomalies and dysmorphisms

Question 6

outline how the copy number variation in a chromosome microarray can have different implications

Answer 6

Question 7

example of a single nucleotide variant (substitution of one nucleotide for another) can be pathogenic

Answer 7

cystic fibrosis

Question 8

example of how an Intragenic CNVS: deletion or duplication of one or more exons within a gene can be pathogenic

Answer 8

duchenne muscular dystrophy

Question 9

example how a triplet repeat expansion (

can be in non-coding part of gene (Fragile X) or in the coding part of the gene (huntington)) can be pathogenic

Answer 9

fragile X syndrome

Question 10

Indications for Exome or large panel GENE sequencing

Answer 10

Patients with a presentation where there is high genetic heterogeneity.

Patients where there is a high suspicion for a genetic disorder, but the clinician is unable to narrow down the cause.

Question 11

WHen to order gene panel (slightly more targeted) vs gene exome sequencing (entire genetic make up)

Answer 11

panel for breast cancer; ex/ looking only for genes correlated with the specific disesaes)